Basic fibroblast-growth factor (bFGF) is a polypeptide mitogen for endothelial cells and a variety of other mesenchymal cells. It also speeds wound healing and produces angiogenesis in bioassays, but it is not known whether the results of adding FGF mean that FGF is involved in these functions naturally. It is not known what regulates FGF transcription, translation or release. Considerable evidence suggests that hypoxia can promote angiogenesis and many mechanisms have been proposed for this effect. One possibility would be that hypoxia promotes the release of basic FGF from hypoxic or ischemic tissue. Since endothelial cells synthesize FGF, at least in culture, they could be the cellular source of FGF. To examine this possibility we subjected confluent mouse lung capillary endothelial cells to 5% oxygen for 3 hours a day for 4 days. This stimulus did not cause cell death or an increase or decrease in replication. However, it increased the growth activity in the conditioned medium for 3T3 fibroblast. The increase was found in the fractions that eluted at 0.5 and at 2.0 of MNaC1, which is consistent with an increase in PDGF and basic FGF in the conditioned medium of the hypxic cells. The cell lysates also showed increases in these fractions. Confirmation of the identity of the 2.0 M fractions was obtained with a competitive equilibrium radioimmunoassay, using an antiserum raised against the first 24 amino acids of basic FGF. These results are consistent with either an increase in the synthesis and release of these peptides or possibly a decrease in their proteolytic degradation, both within cells and in the medium, in response to hypoxia and its concomitant acidosis. These findings are of potential relevance to wound healing, tumor growth and the development of collaterals in response to myocardial ischemia or infarction.